Novel metabolic pathway of phenols catalyzed by cytochrome P450 and its mechanism

Research output: Contribution to journalArticle

Abstract

We have found a novel metabolic pathway of phenols catalyzed by cytochrome P450 and its chemical models. When various p-substituted phenols (substituent = OPh, NO2, CN, CH2OH, COCH3, COPh, COOH, F, Cl, and Br) were reacted with rat liver microsomes system or meso-tetraphenylporphinatoiron(III) chloride model system, the substituent was eliminated to produce hydroquinone. In the case of p-cresol, p-toluquinol was formed instead of hydroquinone. To elucidate how the substituent is eliminated, we attempted to detect the product derived from the eliminated group. Results indicated that the mechanism of this reaction can be divided into two types: the substituent is eliminated as an anion and as a cation. P450 also catalyzed phenol coupling reaction to give biphenyl derivatives, diphenyl ether derivatives, and dibenzodioxin.

Original languageEnglish
Pages (from-to)1202-1209
Number of pages8
JournalYuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
Volume58
Issue number12
Publication statusPublished - 2000 Dec

Fingerprint

Phenols
Cytochrome P-450 Enzyme System
Derivatives
Phenol
Liver
Anions
Cations
Rats
Chlorides
hydroquinone
Metabolic Networks and Pathways
4-cresol
dibenzodioxin
iron tetraphenylporphyrin
phenyl ether
2-methyl-1,4-hydroquinone
diphenyl

Keywords

  • Cytochrome P450
  • Cytochrome P450 model
  • Dibenzodioxin
  • Drug metabolism
  • Estrogen
  • Phenol coupling
  • Phenol metabolism

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

@article{945ac01b13f04b0c85d98b9a786e8ffd,
title = "Novel metabolic pathway of phenols catalyzed by cytochrome P450 and its mechanism",
abstract = "We have found a novel metabolic pathway of phenols catalyzed by cytochrome P450 and its chemical models. When various p-substituted phenols (substituent = OPh, NO2, CN, CH2OH, COCH3, COPh, COOH, F, Cl, and Br) were reacted with rat liver microsomes system or meso-tetraphenylporphinatoiron(III) chloride model system, the substituent was eliminated to produce hydroquinone. In the case of p-cresol, p-toluquinol was formed instead of hydroquinone. To elucidate how the substituent is eliminated, we attempted to detect the product derived from the eliminated group. Results indicated that the mechanism of this reaction can be divided into two types: the substituent is eliminated as an anion and as a cation. P450 also catalyzed phenol coupling reaction to give biphenyl derivatives, diphenyl ether derivatives, and dibenzodioxin.",
keywords = "Cytochrome P450, Cytochrome P450 model, Dibenzodioxin, Drug metabolism, Estrogen, Phenol coupling, Phenol metabolism",
author = "Tadahiko Mashino",
year = "2000",
month = "12",
language = "English",
volume = "58",
pages = "1202--1209",
journal = "Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry",
issn = "0037-9980",
publisher = "Society of Synthetic Organic Chemistry",
number = "12",

}

TY - JOUR

T1 - Novel metabolic pathway of phenols catalyzed by cytochrome P450 and its mechanism

AU - Mashino, Tadahiko

PY - 2000/12

Y1 - 2000/12

N2 - We have found a novel metabolic pathway of phenols catalyzed by cytochrome P450 and its chemical models. When various p-substituted phenols (substituent = OPh, NO2, CN, CH2OH, COCH3, COPh, COOH, F, Cl, and Br) were reacted with rat liver microsomes system or meso-tetraphenylporphinatoiron(III) chloride model system, the substituent was eliminated to produce hydroquinone. In the case of p-cresol, p-toluquinol was formed instead of hydroquinone. To elucidate how the substituent is eliminated, we attempted to detect the product derived from the eliminated group. Results indicated that the mechanism of this reaction can be divided into two types: the substituent is eliminated as an anion and as a cation. P450 also catalyzed phenol coupling reaction to give biphenyl derivatives, diphenyl ether derivatives, and dibenzodioxin.

AB - We have found a novel metabolic pathway of phenols catalyzed by cytochrome P450 and its chemical models. When various p-substituted phenols (substituent = OPh, NO2, CN, CH2OH, COCH3, COPh, COOH, F, Cl, and Br) were reacted with rat liver microsomes system or meso-tetraphenylporphinatoiron(III) chloride model system, the substituent was eliminated to produce hydroquinone. In the case of p-cresol, p-toluquinol was formed instead of hydroquinone. To elucidate how the substituent is eliminated, we attempted to detect the product derived from the eliminated group. Results indicated that the mechanism of this reaction can be divided into two types: the substituent is eliminated as an anion and as a cation. P450 also catalyzed phenol coupling reaction to give biphenyl derivatives, diphenyl ether derivatives, and dibenzodioxin.

KW - Cytochrome P450

KW - Cytochrome P450 model

KW - Dibenzodioxin

KW - Drug metabolism

KW - Estrogen

KW - Phenol coupling

KW - Phenol metabolism

UR - http://www.scopus.com/inward/record.url?scp=21144437856&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=21144437856&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:21144437856

VL - 58

SP - 1202

EP - 1209

JO - Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry

JF - Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry

SN - 0037-9980

IS - 12

ER -